Scoring 35 in the Bonus Points System (BPS), Rodriguez was afforded a rare opportunity up front and responded with a goal and assist.
He also made five recoveries and completed 83% of 30 attempted passes as the visitors ended a three-match goalless streak.
Middlesbrough's Patrick Bamford (£4.9m) received two bonus points, with 26 in the BPS.
Stationed on the right wing in his first Premier League start for Boro, Bamford scored the hosts' consolation goal and made three recoveries.
Nathan Redmond (£5.9m) claimed a single bonus point for the visitors.
The Saints attacker recorded a BPS tally of 23 after emerging from the bench at the break to net a second-half winner for Claude Puel's men.
Bamford earned top spot in the ICT Index with a score of 13.6 - comfortably his best of the campaign.
An impressive Threat score of 84 underpinned that total, with Bamford enjoying more touches in the opposition penalty area than any other player, firing four close-range efforts.
Rodriguez ranked second in the Index with a score of 9.9.
Listed as an FPL midfielder, the versatile attacker had just three touches in the Middlesbrough penalty area - each one a shot on goal.
Having last started a Premier League match in Gameweek 30, Rodriguez was barely considered as an FPL target ahead of the Gameweek 37 fixtures.
However, Southampton’s busy schedule meant that Puel made seven changes to his line-up.
Jack Stephens (£4.2m and 40,000+ transfers in), Manolo Gabbiadini (£6.6m and 27,000+) and Cedric Soares (£4.9m and 19,000+) were all subject to significant investment ahead of Friday evening’s deadline.
They will push for a return for Wednesday’s visit of Manchester United, although many of Gabbiadini's owners have already parted company.