The two sides will meet in the Bernabeu on Wednesday evening, with the return leg penned in at Old Trafford for early March.
While many have tipped ex-United winger Ronaldo to be the difference between the teams, Owen believes that the Red Devils are capable of dealing with the Portuguese attacker.
"Ronaldo is the best player on the pitch, but United would have the second and third best players," he told Sky Sports News. "If anyone is going to stop him it would have to be United who have had him on their books for many years and they will know his strengths and weaknesses.
"On the flip side of that you have Rooney in form and Van Persie scoring freely. I think United could have the edge."
Owen was part of the United squad the last time they reached the final of the competition back in 2011 when they were defeated 3-1 by Barcelona.