Motherwell went into the game unbeaten in the last eight, while Hamilton had won six in a row - a run of form that had seen both sides level on points and pushing for a top-six slot.
Accies came out of the traps quickly and could have been ahead after only five minutes.
James McArthur's 25-yard shot deflected off the head of Kenny Deuchar but the Well keeper Graeme Smith managed to change direction and claw the ball away for a corner.
From the resultant corner, Hamilton had the ball in the net thanks to a Simon Mensing's overhead kick but referee Dougie McDonald somehow saw a handball and disallowed the effort.
It had been all Accies for much of the half with Alex Neil and James McCarthy firing just wide.
Motherwell had little to offer at the other end apart from a Stephen Hughes' cross into the six-yard box which was narrowly missed by Cillian Sheridan.
It was therefore a shock when Motherwell took the lead with their first real effort on target in the 45th minute.
Steven Hammell's cross was flicked on by Sheridan into the path of David Clarkson, who kept his cool to prod home from close range.
Halfway through the second half, Graeme Smith pulled off another fine save to keep his side in the lead after beating out an angled drive from Neil.
Hamilton made three substitutions in an effort to find an equaliser but this led them vulnerable to the counter-attack and it was Sheridan who came closest as he clipped a shot wide at the front post.
The home side were then denied what looked a clear penalty when Tomas Cerny pulled down Paul Quinn as the full-back tried to round the keeper but the referee gave only a goal-kick.
In the end it was Clarkson's goal that was enough to extend Motherwell's unbeaten run to nine games and put them level with the team currently in sixth.