Guo finished with 488.1 points, with France's Celine Goberville claiming silver in a shootoff with Ukraine's Olena Kostevych after both finished on 486.6.
Guo threw her hands over her face in disbelief after scoring a 10.8 - just shy of the maximum 10.9 - to overhaul Goberville, who held a 0.5 advantage going into the 10th and decisive round.
The 25-year-old Frenchwoman was only able to muster a disappointing 8.8 with her final effort.
"I just focused on doing my best with the final shot," an elated Guo said after winning China's second shooting gold of the Games.
"It means I'm the best. I am so excited. I was just focusing on the competition and not on the others."
The 28-year-old Chinese had topped the qualifying with a score of 388 out of 400 from her 40 shots to reach the eight-woman final at the Royal Artillery Barracks in south east London, but began the final nervously.
In front of a packed crowd in the indoor shooting range, the Chinese fired a woeful 8 to open the door to her European counterparts, who both finished with 387 in qualifying.
Kostevych, the 2004 Athens Games gold medallist, then took advantage after the first round with a 10.1 and she shared the lead with Guo and Goberville after the second.
Guo and Goberville then exchanged the lead, with the Chinese struggling to replicate the Frenchwoman's consistency.
Goberville reeled off five scores of 10.1 or better to take a 0.5 point advantage into the final round, only to produce her worst shot of the day, an 8.8, to surrender the lead.
"The last shot - it was a mistake, I cannot explain it," Goberville said after winning France's first medal of the London Games.
"I was already very stressed... I had difficulty realising where I was, what was happening.
"After the last shot I was pretty disappointed but I knew I had a medal. I was disappointed that I had gone from first to second with my last shot but then I had to concentrate on the shootoff."
Guo's victory followed countrywoman Yi Siling's triumph on Saturday when she won the first gold of the Games in the 10m air rifle as China made a strong start to London 2012.
As Guo celebrated her victory with her coaches, the crowd were hushed before Goberville struck a 10.6 in the shootoff to trump Kostevych's 9.7 and seal silver.
The women's skeet final on the outdoor range was due to take place at 1300 GMT despite rain, with organisers saying the event would not be postponed unless there was a threat of thunder and lightning.