Meghan, 36, is passing another royal milestone, days after her first balcony appearance on Buckingham Palace on Saturday, during Trooping the Colour.
She and the Queen cut the ribbon to open the bridge over the Mersey and unveiled a plaque to commemorate the event.
The opening took place at the Catalyst Museum, which offers a bird's eye view of the new crossing from the glass top observation gallery.
This is her first event without her husband, Prince Harry, by her side.
The Queen and Meghan arrived by Royal train before travelling by car to the bridge, a £1.86bn project, which should ease traffic between Runcorn and Widnes.
They were greeted by local dignitaries as the street around Runcorn station was lined by schoolchildren and well-wishers who waved flags and applauded as they arrived.
Queen Elizabeth wore a striking green outfit and hat for the event, as the country remembers the victims and survivors of the Grenfell tower fire by going green for Grenfell.
After the unveiling and ribbon cutting, Meghan and the Queen will watch a performance by local schoolchildren called Bringing Communities Together.
The pair will then go to Chester for further engagements.
Meghan married Prince Harry in Windsor in May and since then, has joined the royal family for Trooping the Colour, also known as the Queen's birthday parade, and has announced her first royal tour.
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The Duke and Duchess of Sussex are to make an official visit to Australia, New Zealand, Fiji and the Kingdom of Tonga in the Autumn.