Fisher also shot 68 on Saturday for a 12-under 204. Fellow Englishman Paul Casey had a 66 to trail Mickelson by three. Kevin Stadler, who had a one-stroke lead after two rounds, slipped to a 73 and fell four behind Mickelson.
Five players were in a group seven shots back including Vijay Singh (72), defending British Open champion Padraig Harrington (69) and defending tournament champion Yang Yong-eun (70) of South Korea.
Mickelson, who finished 16 strokes behind winner Angel Cabrera last weekend in the Singapore Open, is finally producing some good golf at the Sheshan Golf Club in Shanghai, an American-style layout graced by an Italian-accented clubhouse.
It's Mickelson's first event in China and his first foray into Asia. He plans to head home after Sunday's final round.
A victory would only be his second out of the United States. The other came 13 years ago in France.
'I want to play well whether it's the States, whether it's here,' Mickelson said. 'I want to compete and I want to have a chance to win. To me that's what's fun. It's difficult to come this far and not play well.'
Mickelson made several 5-foot putts to save par during the round. However, a 35-footer for birdie on No. 15 put him in the lead for good, a difficult two-tier green with a rolling slope.
'I certainly didn't expect to make it,' Mickelson said. 'It was such a long putt, you can't plan on making those and I was fortunate to see that one go in.'
He also missed a 30-foot eagle putt on the final hole and settled for an easy birdie to push him two ahead.
'Tomorrow, I hopefully will have more birdie opportunities, which will be the goal to not have to fight for par as much,' he said.
Fisher, who picked up his first victory on the European tour in the Dutch Open earlier this year, looked comfortable playing in the final pairing with Mickelson and Stadler. He was in the final pairing with Tiger Woods earlier in the season in the Dubai Desert Classic.
'Tiger was fantastic,' Fisher said. 'I was shocked at how open he was. We were chatting like we were best friends. And the same today with Phil. He was very polite, we were chatting most of the way around. It kind of really helped me to relax.'
Fisher said the easy camaraderie convinced him of something. 'I'm good enough to be out here with these guys, so why not try to show them how good I am.'