You may be interested in my answer on the Mixton War in our Native American Revolt, Rebellion, and Resistance - Panel AMA almost a year ago. The Mixton War was an uprising by Native groups in the Jalisco region against the Spanish and their atrocities. These groups were initially successful in driving the Spanish out of the immediate area. This may be because the Spanish were unable or unwilling to learn the differences in the numerous cultures and languages which allowed Native agents to freely operate in the open and organize their rebellion against Spanish rule. Unfortunately, the Spanish were able to recruit a force of tens of thousands of Aztec and Tarascan allies which they used to storm the fortified hilltop fortresses of the rebels. Once the main fortresses were conquered the back of the rebellion was broken. Other groups held out for as long as they could, but either retreated into the mountains or were subdued. Some groups like the Cora were able to resist Spanish rule in Nayarit until 1721 when a combination of disease and drought forced the Cora to surrender. Other groups joined up with Chichimec groups to fight in the Chichimeca War of 1550 to 1590.

Edit: Wanted to re-write a very awkwardly done sentence. Also added an 'Aftermath' section in case anyone is interested as to what happened after Isandlwana.

Since you haven't clarified which geographical area, I feel safe in telling you about the resistance of the Zulu kingdom to British settlement of modern-day South Africa in the late 19th century.

CONTEXT:

The British had long been interested in the colonization of South Africa, and had for decades been pushing the originally Dutch settlers farther out of the Dutch claim through cessions given by the Dutch government originating with the giving up of Cape Town in the 1814 and ending in a series of two conflicts called the Anglo-Boer Wars.

The Dutch maintained some relations with the greatest native regional power, the Zulu empire, trading firearms and European goods for cattle, but viewed the Zulu king Cetshwayo kaMpande as a constant threat. The British had far less interest in maintaining good relations, and after the discovery of diamonds in 1867, were itching for an excuse to go to war against the Zulu. After a few border disputes and raids carried out by Zulu, the High Commissioner of the Cape Town colony, Sir Bartle Frere, issued an ultimatum in 1878 to the Zulu king which entailed, amongst other thing, that his army be disbanded, his firearms be confiscated, and that the Zulus accept a British diplomat to ensure every change was properly enacted. He knew the Zulu king would refuse, which he did, and proceeded to mobilize.

BRITISH DEFEAT:

Lord Chelmsford was the Commander-in-Chief of the British forces, who arrogantly assumed that the Zulu would not even engage him in open battle. He split his 15,000 soldiers into five columns in the hopes of surrounding the Zulu's main force. He then took three of his columns and crossed the Buffalo River 11 January, 1879 heading directly for the capital of Ulundi. On January 20, he made camp at Isandlwana.

Here, Chelmsford split his force, taking 2,500 men to pursue what he thought was the Zulu vanguard but was actually a diversionary force, leaving only 1,800 men and two cannon to guard the camp against a rapidly approaching force of 20,000 Zulu. When a detachment of his Natal auxiliary cavalry were on a scouting mission, they crested a hill only to be met with this massive Zulu force crouching in complete silence, awaiting a signal that was supposed to come several days later once they were certain that Chelmsford was too far away to give aid. Realizing they had been spotted, they leaped into action. The camp had nothing in the way of defenses. Chelmsford hadn't even ordered his men to circle the wagons in the customary fashion when they arrived and made camp, thinking that the week or so it would was take too long and that they would be marching off sooner than that anyway. As such, the 1,800 men were caught out in the open and could do little more than form an ad-hoc battle line. The Zulus were quick to overwhelm them, and after four hours of vicious fighting in isolated pockets, 1,300 British including 52 officers lay dead. The Zulus had roughly 1,000 dead and 2,000 wounded.

The shock of this was that the Zulus were equipped with short spears, cowhide shields, and outdated muskets and rifles that they had little discipline with in comparison to their well-drilled but (in this case) poorly led foe. The British on the other hand were equipped with state-of-the-art breech-loading Martini-Henry rifles and modern cannon, but it wasn't enough to stop the onslaught. To this day the battle remains as the greatest defeat that a modern army has ever suffered to a technologically inferior force.

AFTERMATH:

After losing such a sizable part of his force, Chelmsford retreated back into British territory in order to re-group and re-think his strategy. With reinforcements arriving, soon to total 16,000 British and 7,000 Native troops, Chelmsford re-organized his forces and again advanced into Zululand in June, this time with extreme caution building fortified camps all along the way to prevent any repeat of Isandlwana. Cetshwayo could see the writing on the wall, and sued for peace, but his pleas were ignored by Chelmsford who wanted to restore his fractured honor. On July 4th 1879, he marched on the capital of Ulundi, killing 500, wounding 1,000, and losing about 15.

In short, the Zulus were not a people to be trifled with and the British paid dearly for their arrogance, but in the end the gross technological differences won out and the Zulu empire was defeated.

SOURCES:

Colenso, Frances E. (1880). History of the Zulu War and Its Origin. Assisted by Edward Durnford. London: Chapman & Hall.

Barthorp, Michael (2002). The Zulu War: Isandhlwana to Ulundi. Weidenfeld & Nicolson. ISBN 0-304-36270-0.

Knight, Ian (2003). The Zulu War 1879. Osprey. ISBN 978-1-84176-612-6.

Clarke, Sonia The Invasion of Zululand, Johannesburg, 1979.

This may not qualify as significant but it's a neat piece of Texas history.

In Spanish Texas, the Spanish established a mission and presidio on the San Saba River for the Apaches in 1757. The Apaches seem to have done this to gain the aid of the Spanish in attacking the Comanche. The Comanche saw this as an alliance between Spain and the Apaches. About 2,000 Comanches and their allies destroyed the mission entirely in 1758. The natives then marched to the presidio and tried to get the soldiers to come out from behind the walls. The Spanish didn't leave the safety of the fort and the natives dispersed.

The Spanish responded by sending troops from the presidio and from San Antonio to retaliate against the natives. They ended up retreating back to their fort. For the next decade, the Comanche attacked nearly every single patrol sent out from the fort. At one point, the commander of the fort writes "The enemy [is] so superior ... in firearms as well as in numbers, that our destruction seems probable."

Spain did not want to admit any defeat and kept the fort open for 10 more years, despite the fact that the Comanches basically hunted down every Spanish soldier that dare set foot outside the walls. When the presidio was closed in 1769, this area of Texas was abandoned by the Spanish.

Sources: Weber, David J. (1992), The Spanish Frontier in North America, Yale Western Americana Series

Chipman, Donald E. (1992), Spanish Texas