Following the disappearance and murder of her daughter several years ago, Ms Rodríguez was actively engaged in supporting families of disappeared persons.
Rodríguez, 50, was killed on the day Mexico celebrates Mother's Day, which the United Nations noted gives the murder "a chilling symbolism".
The human rights group Amnesty International said Rodriguez "led the search for her daughter and thousands more in Tamaulipas".
Miriam Rodriguez Martinez was shot multiple times on Wednesday night at her home in the town of San Fernando in Tamaulipas state. She returned to look for her and did not stop until she found her remains two years later in an unmarked grave.
He added that nine people had been put on trial for her daughter's kidnapping and murder.
Mexico's national human rights commission (CNDH) condemned the murder, saying it underscored the government's failure to keep the public safe and protect human rights advocates.
Rodriguez's group said she had succeeded in identifying her daughter's killers and getting them brought to justice.
"Mexico has become a very risky place for those who have the courage to devote their lives to search for missing persons", said Erika Guevara Rosas, Amnesty International director for the Americas, according to Reuters, referring to the latest tragedy.
"The nightmare they face not knowing the fate or whereabouts of their relatives and the dangers they face in their work, which they perform given the negligent response from the authorities, is alarming", she said.
Protests to clarify the cases of Mexico's estimated 30,000 or so disappeared - many abducted during the country's more than decade-long war on drugs - took place throughout Mexico on Wednesday, the same day that Rodriguez was slain.
"I express my energetic condemnation for the cowardly murder of the activist Miriam Rodriguez", Tamaulipas Gov. Francisco Javier Cabeza de Vaca said in a Twitter message.