Kightly scored direct from a left-wing free-kick in the 17th minute and Ebanks-Blake made the game safe 23 minutes into the second half to earn Wolves their seventh successive Championship win and sentence City to their first away defeat
in the league this season.
It was not the way that City boss Gary Johnson had hoped to celebrate signing a new five-year contract the day before the game, but history was against his side picking up a victory as they have not at Molineux since 1931.
They had their chances but could not find a way past Carl Ikeme, while Wolves would have raced to a bigger win but for City goalkeeper Chris Weale, who produced two stunning saves at the start of the second half.
City had received two warnings before Kightly's strike with David Jones firing on to the roof of the net and Andy Keogh heading wide.
But their luck ran out when Cole Skuse fouled Matt Jarvis just in from the left touchline.
Kightly swung the free-kick into a crowded area and Weale could only stare in disbelief as the ball flew directly over him and into the far corner of the net.
While it was a fortunate way to take the lead, Wolves had to ride their luck to take the advantage into half-time.
Ikeme, who was making his first Championship start, did well to stop a 20th minute drive from Ivan Sproule.
Ikeme then picked up a Richard Stearman back pass and, from the resulting free-kick, Michael McIndoe's fierce drive was blocked by Stearman.
Ikeme was by far the busier of the two keepers in the opening period and he acrobatically tipped a Dele Adebola header over the bar on the half-hour before diving low to save Nicky Maynard's shot on the turn 10 minutes later.
Having survived the City onslaught, Wolves would have made the game safe in the opening ten minutes of the second half only for Weale to tip a Jones header over the bar and then deny Ebanks-Blake with a point-blank save.
But Ebanks-Blake was not to be denied a fifth goal of the season and his persistence was rewarded in the 68th minute when City failed to fully clear a Jarvis cross.
Jones headed the ball goalwards and Ebanks-Blake pounced spectacularly with an acrobatic overhead kick from six yards.