Argentina midfielder Dario Conca opened the scoring in the first half and set up another for substitute Wu Pingfeng in the second period at Shanghai Hongkou Stadium.
The win edged promoted Guangzhou a step closer to the title as they extended their advantage over second-placed Beijing Guoan to 15 points with seven games to go.
Guangzhou attacked from the outset with Brazilian striker Muriqui causing the Shanghai defence plenty of problems.
He was the architect of Guangzhou's opener after 16 minutes, clipping a cross into the path of Conca, who fired past goalkeeper Wang Dalei.
Luis Salmeron latched onto Wu Xi's cross from the left but blasted wide in what proved to be Shanghai's best chance before Wu doubled the lead in the 56th minute when he was picked out unmarked by Conca.
The hosts suffered a further setback 18 minutes before the end when defender Cheng Liang was sent off for elbowing Muriqui but Guangzhou were unable to add to their lead.
"I should give credit to my players as they were fully concentrated on the match and overcame injury problems," said Guangzhou's Korean manager Lee Jang-soo.
"There are still seven games left and we should keep our focus in each of the contests to achieve the best results."
Meanwhile, nearest challengers Beijing Guoan lost 2-1 at Changchun Yatai.
Senegal striker Ladji Keita fired the visitors ahead after nine minutes at Changchun Jingkai Stadium but Wang Dong levelled nine minutes later.
Brazilian forward Claudinei Alexandre Aparecido then clinched victory for Changchun 20 minutes before the final whistle, heading Wang's inviting cross into the net.
Elsewhere, Chengdu Blades and Shenzhen Ruby played out a 2-2 draw, Henan Jianye defeated Liaoning Zhongyu 2-1 and Shandong Luneng lost 1-0 to Qingdao Zhongneng.
Tianjin Teda outclassed Nanchang Bayi 3-0, Dalian Shide saw off Shaanxi Chanba 3-1 and Jiangsu Shuntian got the better of Hangzhou Greentown 2-0.