A header from Connor Goldson and Borna Barisic’s free-kick added to the rout as Steven Gerrard’s men moved two points above their Glasgow rivals.
Celtic’s shock defeat at Livingston earlier on Sunday handed Steven Gerrard’s team the chance to hit the summit for the first time this season and they came out in determined fashion.
Hamilton had already survived several dangerous balls into their box before being cut open by Greg Stewart’s through ball in the seventh minute.
Defoe chipped the ball over the diving Owain Fon Williams and in off the post.
Accies survived a torrid opening 20 minutes without conceding again with Sheyi Ojo and Stewart coming close from long range, and they had a major let-off when Defoe volleyed against the post from four yards following a quickly-taken corner.
Hamilton were crowding their penalty box but Rangers had the freedom to spread the ball about in front of them, and Goldson doubled their lead in the 34th minute after a long-range one-two.
The centre-back started running after passing the ball out wide to James Tavernier from midway inside the opposition half and dived to head home his captain’s cross from six yards.
“We shall not be moved” rang out around Ibrox and it was clear Hamilton were not going to threaten that assertion, although Ronan Hughes fired just over after Goldson’s goal.
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