The world and European heptathlon champion, competing for the first time since an ankle tendon problem ruled her out of the European Indoor Championships and left her unable to run for seven weeks, clocked 12.88 seconds for the 100 metres hurdles in rainy and windy conditions on a raised track on Deansgate.
The 25-year-old was awarded third place, ahead of her American-born Great Britain team-mate Tiffany Ofili, who broke her British indoor record earlier this year and was given the same time.
Ennis finished behind hurdles specialists Ginnie Crawford and fellow American Danielle Carruthers, who won in 12.73secs.
Ennis was less impressed with her 17.40s run in the 150m after a poor start, Abi Oyepitan winning in 17.34, but it was her return to fitness which pleased her most.
"One massive positive to take from the day is that my ankle feels good," she said.
"It's a bit of a relief to be back in competition and I'm just excited about the season now.
"If someone had said two weeks ago that I would be in Manchester running that sort of time (in the hurdles), I would have been very happy with that. So I'm glad I did it and now I can move on.
"To get into this shape so quickly is quite promising."
Ennis, who is due to compete in the javelin in the Loughborough International next Sunday, now has her sights set on her first heptathlon of the season at the Hypo-Meeting in Gotzis, Austria on May 28 and 29.
Her coach Toni Minichiello, though, warned not to expect too much too soon.
"If you are expecting her to go there and spank people and score huge scores and a personal best, I'd say I don't think that's the case," he said.
"I think she can go there and be competitive, but she will be up against everybody in Gotzis so she'll be nervous to see whether she's on her game."
Tyson Gay won the 150m in 14.51s, some way off Usain Bolt's world best of 14.35.
It was, though, the American's first outing of the season, while he said beforehand he was only 80 per cent fit and the conditions were hardly conducive to fast times.
"I've missed a lot of training this year because of a couple of little niggles and injuries so I'm pretty impressed with my performance," said Gay. "I'm feeling OK. I'm a little bit sore, but nothing major. I'm feeling pretty good. I came through the first 100m in 9.91, that's kind of where everyone else is in the world right now so that's not bad.
"I'm satisfied with my time, I think it's pretty fast, but I've just got to stay healthy and be ready."
Elsewhere, European and Commonwealth 110m hurdles champion Andy Turner continued to his fine start to the season with a double victory, also winning the 200m hurdles.
The Nottingham athlete, who earlier this month equalled the fastest time he ran last year with a 13.28 run in Jamaica, won the 110m hurdles in 13.41 and clocked a time of 22.10 over the longer distance.
Olympic 400m champion Christine Ohuruogu, looking to put an injury-ruined 2010 behind her, was well off the pace as she finished fourth in the 200m in 24.48, American Allyson Felix winning in 22.12.
Other winners included Mark Lewis-Francis and Jeanette Kwakye in the 100m and France's Martial Mbandjock in the 200m.