It's more complicated than just saying "isolationism," though isolationism is definitely a factor.

Wilson and the Democratic Party lose ground in the 1918 midterm elections, and critically, the Republicans gained six seats in the Senate, giving them a two seat majority there. Now, not all Republicans were united in their opposition to the treaty, but a lot of them have some kind of reservation about the treaty and whether or not the provisions about collective security would supersede the constitution; their nightmare scenario is one in which Congress would not enjoy the prerogative to declare war. Among the Republicans, the leader on this issue is Henry Cabot Lodge, who supports the League of Nations and by extension the Treaty of Versailles, but with reservations. Namely, he wants to limit Article X, which requires the United States to militarily support a treaty signatory who is attacked.

Then you have the so-called Irreconciliables, who categorically oppose the League and the treaty. Some are Democrats, but most are Republicans, and there are 13 of them. One of the more prominent ones is William Borah of Idaho, a Republican who comes closest to matching a genuine isolationist stereotype. He only supported the war because of the effects of unrestricted submarine warfare on American shipping, and opposed any insinuation of common cause with the Entente. He feels the Treaty and the League is simply an awful idea, and nothing will change his mind.

But the Democrats are also not of one mind about the treaty. The Democratic Party is a funny institution in this period because it's composed (largely) of rural Southerners and then urban, northern immigrants. Two of their largest sources of support in ethnic communities are A: the Irish, and B: the Germans. The Irish have no love lost for the British Empire, and it's floated by some that those same collective security provisions could lead the Americans to going to war on behalf of Great Britain should Ireland rebel (which it did, though the legal logic here has always struck me as tangled; in any event, some Irish-Americans really feared this). The German-Americans don't like it because they feel it's unduly harsh to Germany. This peels away a number of Democratic senators.

Then, on top of those divisions, you have Wilson and some of the Democrats who follow suit with him. Wilson proved ill-suited to seeking any kind of compromise on this particular issue; he refused to accept any kind of reservation or amendment to the treaty from Lodge. When he tried to sell the importance of the treaty directly via a speaking tour, he suffered a series of strokes that effectively incapacitated him (some scholars allege that the strain of the tour pushed him too hard). On the one hand, it removes Wilson from much of the discussion and lobbying, but even in the midst of incredible illness, he still refused to allow any perceived weakening of the treaty. A number of Democrats followed suit with him, only assenting to vote for an unmodified Treaty.

What you get out of this is a frankly madcap back-and-forth; majority coalitions are possible, but you need a two-thirds majority to pass a treaty in the Senate, and no configuration of the treaty ever gets to that point. Lodge, with a number of Republicans and Democrats gets close, but it's a modified treaty. Wilson refused to support it, and so did a number of his Democratic supporters, meaning that the vote failed and the treaty was never signed. The U.S. concluded a separate peace treaty with Germany, and never joined the League of Nations.