Family Macahan's is the story of the white man's conquest of the American West, which we follow through family Macahan valiant struggle for survival. It is the story of mountain men who went west to explore the world beyond the next river bend, the fur trappers who nearly extinct buffalo herds, the gold graves searching for El Dorado, about peasants who became wealthy landowners and the simple people who were on the run. There is also a story about the American Indians. Brave and fearless, but hopelessly outnumbered, these primitive people were the ultimate losers in the battle for land in the west.
Kate Macahan's sister, Molly Culhane, joins the family. A Mormon family arrives at the homestead while fleeing religious persecution, but the patriarch soon charms Laura. Zeb mediates between the Army and the angry Sioux after a Russian royalty kills a buffalo on Sioux land. Luke aids a local sheriff and meets his feisty daughter.
Zeb sides with the Sioux after the Russian incident triggers a war - and the clash leads to a great leader's sacrifice. Luke's feelings for Hillary Gant intensify, but when her father learns of Luke's past, he asks Luke to leave. Laura accepts a marriage proposal, while Luke finds himself forced to join a thieving band of ex-Confederates.
Luke's attempt to foil the Flint gang's gold robbery scheme doesn't go as planned. Zeb rescues a woman from two hide-cutters and is surprised to find a love from his past. When a certain guest arrives for Laura's wedding, second thoughts arise. Jessie fights for her life after being stung by a swarm of bees.
With the sheriff's son held hostage by Flint, the robbery goes forward, leaving two men dead. Jessie's condition worsens as the doctor can't help her. Zeb's and Beth's accounts of her rescue come under suspicion by authorities, causing her to leave abruptly, with her leading Zeb to a mountain cabin.
Zeb learns Beth's husband is supposedly a dead, guilt-ridden Army hero involved in a military massacre. As Jessie nears death, Zeb decides to take her to an Arapaho medicine man - with a skeptical Luke and Josh in close pursuit.
Jessie recovers with the help of the Aapaho, but the tribe finds itself on the brink of starvation due to the broken promise of beef shipments. Zeb and Luke embark on a cattle-herding journey across harsh flatlands, joined by contentious Indian drovers - and trailed by a young runaway.
On the journey home, the stagecoach carrying Molly and Jessie is wrecked - and a dazed Jessie wanders into the desert, where she meets the young Navajo Teel-O. Zeb and Josh purchase a cattle herd to bring back to the reservation, and Zeb hires old friend Tap Henry to serve as cook on the drive.
Deek Peasley is reluctantly hired to lead the search party for Jessie, who tries to bridge the language gap with Teel-O. The cattle drive gets underway, shadowed by Tap's rustler cronies. While camping out, tensions mount between Deek and Molly, and a costly bargain is negotiated.
Jessie and Teel-O have a fateful encounter with Teel-O's grandfather. While scouting for water, Luke comes to the rescue of Judge Rensen, who offers to seek a pardon for Luke's criminal past in Missouri. Teel-O and Jessie are stalked be would-be slavers.
Luke is jailed pending his hearing, and from his cell, gives a newspaper interview that draws trouble to Las Mesas. Apaches disrupt the cattle drive. Jessie is rescued, and she and the others return home to find gold in the Machan creek - just as Deek becomes more neighborly.
After he learns of presence of gold, Deek bribes a land agent to seize ownership of the Macahan creek. Tap takes extreme measures to keep Zeb from learning about the rustlers. Josh arrives in Las Mesas to support Luke at the hearing and - literally - runs into Doreen, with whom he is instantly smitten.
A vengeful Stillman hires local power broker Francis Britten to help convict Luke. Deek moves onto Macahan land, and Tap confesses the truth to Zeb. Luke gets a mysterious visitor.
Luke's hearing begins and things look bad for him. Frank Grayson produces proof that Luke was a member of the Flint gang. A snooping Evans overplays his hand with Deek. Josh is framed for assault by Doreen - and his brother's plight provokes Luke to drastic action.
Fleeing jail with Josh, Luke finds Judge Rensen dead. When the brothers split up after narrowly eluding the posse, Josh is attacked and Zeb's pursuit ends in a face off with Stillman. The cattle drive regroups and makes a final homeward push. Deek menaces Laura and Molly for the last time.