Odion Ighalo and Etienne Capoue each had an excellent chance to snatch all three points for the Hornets but both failed to convert from close range as the teams were forced to settle for a point.
Southampton duo Sadio Mane and Victor Wanyama, linked with moves away to Manchester United and Tottenham respectively, both started the fixture but Mane left the field through injury just 25 minutes into the first half.
It means Watford have now drawn all three of their opening matches of the campaign while Southampton find themselves in the relegation zone after two draws and a defeat.
Ronald Koeman succeeded Quique Sanchez Flores in charge at Valencia in 2007 but it is the Watford boss now looking to emulate Koeman, with the Dutchman showing the way in progressing a recently promoted Premier League side, while also bringing European football to the south coast.
How Saints cope with the extra demands of the Europa League is likely to be a crucial factor in whether they can repeat last season’s success and this offered an early indication of the difficulties ahead, coming three days after Thursday night’s first leg draw at home to FC Midtjylland.
The visitors began brightly with Mane, playing just off the striker, making his scintillating pace count in the 16th minute when he raced in behind the Watford backline but Allan Nyom did well to prevent his cross reaching Graziano Pelle.
If Louis van Gaal had been watching over his latest transfer target, he had little else to ponder as the forward was forced off through injury nine minutes later after two collisions with Heurelho Gomes and then Troy Deeney.
The contest was largely a scrappy affair, ridden with heavy touches and speculative balls forward, but the one clear-cut chance in the first half fell to Watford’s Ighalo five minutes before the break.
Deeney fed Ikechi Anya down the right and the Scot fired a low cross to the back post where Ighalo seemed certain to finish from three yards out but the Nigerian failed to connect and Southampton were spared.
Alessandro Diamanti came on at half-time to make his Watford debut but it was Saints who started faster as Pelle’s shot was palmed away from the top corner by Gomes before Shane Long headed the resulting corner over.
The Hornets enjoyed a stronger spell as the game moved past the hour-mark and Capoue should have scored when Deeney flicked to him at the back post but the Frenchman could only head over with the goal gaping.
The hosts looked the more likely to steal a late winner and substitute Ben Watson should have done better with a shot from the edge of the area three minutes from time, but in truth neither side did enough to deserve victory and the spoils were shared.