Needing a win to climb out of the bottom four, Vale created few clear chances and were beaten by goals either side of half-time from Josh Ruffels and Chris Maguire.
Midfielder Ruffels punished a mistake by Vale goalkeeper Deniz Mehmet to fire his first league goal of the season high into the net in the 14th minute after Marvin Johnson's left-footed drive had been parried.
Mehmet then turned aside a ferocious Johnson shot from 25 yards before blocking another effort when the striker ran through on goal.
Chris Eagles shot wide for Vale in the first half after a neat one-two with Rigino Cicilia and in the second, Simon Eastwood tipped Remi Streete's header over the crossbar.
Oxford sealed victory eight minutes from time when forward Maguire hammered the ball home from 14 yards to cap a swift counter-attack.
In the dying moments, Eastwood saved brilliantly from substitute Sam Kelly's shot to ensure a clean sheet for the home side.
Match report supplied by the Press Association.
Match ends, Oxford United 2, Port Vale 0.
Second Half ends, Oxford United 2, Port Vale 0.
Attempt missed. Chris Maguire (Oxford United) left footed shot from the right side of the six yard box misses to the left.
Foul by Rigino Cicilia (Port Vale).
Philip Edwards (Oxford United) wins a free kick on the left wing.
Attempt missed. Sam Foley (Port Vale) header from the centre of the box misses to the right.
Corner,  Port Vale. Conceded by Simon Eastwood.
Attempt saved. Sam Foley (Port Vale) left footed shot from the centre of the box is saved in the top left corner.
Attempt saved. Chris Maguire (Oxford United) left footed shot from the left side of the box is saved in the top centre of the goal.
Corner,  Oxford United. Conceded by Deniz Dogan Mehmet.
Nathan Smith (Port Vale) wins a free kick in the defensive half.
Foul by Kane Hemmings (Oxford United).
Corner,  Port Vale. Conceded by Charlie Raglan.
Attempt saved. Marvin Johnson (Oxford United) left footed shot from outside the box is saved in the centre of the goal.
Goal!  Oxford United 2, Port Vale 0. Chris Maguire (Oxford United) right footed shot from the right side of the box to the centre of the goal.
Attempt missed. Sam Kelly (Port Vale) left footed shot from outside the box is close, but misses to the right.
Attempt saved. Nathan Smith (Port Vale) header from the centre of the box is saved in the centre of the goal.
Attempt saved. Chris Eagles (Port Vale) right footed shot from outside the box is saved in the centre of the goal.
Corner,  Port Vale. Conceded by Simon Eastwood.
Attempt saved. Dan Turner (Port Vale) right footed shot from the left side of the box is saved in the bottom left corner.
Foul by Remie Streete (Port Vale).
Charlie Raglan (Oxford United) wins a free kick in the attacking half.
Corner,  Port Vale. Conceded by Joe Skarz.
Foul by Dan Turner (Port Vale).
Curtis Nelson (Oxford United) wins a free kick in the attacking half.
Attempt missed. Philip Edwards (Oxford United) header from the centre of the box misses to the right.
Corner,  Oxford United. Conceded by Ryan Taylor.
Corner,  Oxford United. Conceded by Danny Pugh.
Attempt blocked. Conor McAleny (Oxford United) right footed shot from the left side of the box is blocked.
Substitution, Port Vale. Anthony de Freitas replaces Scott Tanser.
Attempt missed. Chris Maguire (Oxford United) right footed shot from outside the box misses to the left.
Attempt saved. Josh Ruffels (Oxford United) right footed shot from the centre of the box is saved in the top centre of the goal.
Remie Streete (Port Vale) hits the bar with a right footed shot from very close range.
Nathan Smith (Port Vale) wins a free kick in the attacking half.
Foul by Kane Hemmings (Oxford United).
Attempt missed. Kane Hemmings (Oxford United) right footed shot from the left side of the box is close, but misses to the left.
Substitution, Oxford United. Kane Hemmings replaces Robert Hall.
Substitution, Oxford United. Chris Maguire replaces Joe Rothwell.
Corner,  Port Vale. Conceded by Charlie Raglan.
Nathan Smith (Port Vale) wins a free kick in the attacking half.
Port Vale's League One relegation fears increased as they lost to Oxford at the Kassam Stadium.