Despite declining health, EBW presided at seven Relief Society board meetings in early 1921 and occasionally made comments. The general board cooperated with the family of Zina D. H. Young to commemorate the centenary of her birth on 31 January with a party held in the parlors at Relief Society headquarters. In the middle of a discussion of the proper way to stitch ceremonial clothing for use in Latter-day Saint temples, EBW “exhorted the members of the General Board not to worry over small details with regard to the temple clothing. She stated that if any slight mistakes are made by the people, that the Lord will have mercy upon them.” Because EBW was ill in early February, board members felt inclined to reduce the size of the usual birthday celebration in her honor. However, when she rejoined the board for a meeting on 24 February and was given the option of celebrating with a small luncheon or a large reception, she chose the reception. It was held on the mezzanine of the Hotel Utah on 28 February. Counselor Clarissa S. Williams described the event as “one of the most remarkable receptions the board has ever given,” in part because the many who came included descendants of early pioneers and church founders as well as present-day civic and church friends.

The spring general Relief Society conference was held 1 and 2 April. Before the general sessions on Saturday, 2 April, President Heber J. Grant and his counselor Anthony W. Ivins paid a visit to EBW at the home of her daughter Annie Wells Cannon, where she was now living. President Grant told EBW he would release her and appoint her counselor Clarissa S. Williams as the new Relief Society general president. This break with precedent—Relief Society general presidents since Eliza R. Snow had served until death—was a painfully emotional encounter for all, especially EBW. During the two Saturday sessions of the conference, President Grant reorganized the general Relief Society leadership. All presidency and board members were released, and a new presidency was presented for a sustaining vote—Clarissa S. Williams as president, with Jennie Brimhall Knight and Louise Yates Robison as counselors. Amy Brown Lyman, who had served as general secretary in EBW’s administration, was sustained as secretary-treasurer. After consultation with the new presidency, President Grant also presented the names of board members for a sustaining vote, several of whom had served on EBW’s board. In their remarks, President Grant and other speakers paid tribute to the “faithful labors” of EBW over the years.

Early on the morning of 25 April, EBW quietly slipped from mortality in the home of her daughter Annie Wells Cannon while her daughter Belle Whitney Sears sat at her side. Friends brought flowers and viewed the deceased president, dressed for burial in her temple robes, at the Cannon home, then joined in services at the Salt Lake Tabernacle on Friday, 29 April. Speakers at her funeral included Clarissa S. Williams, Dr. George W. Middleton, Dr. Seymour B. Young, Bishop Charles W. Nibley, Elder Orson F. Whitney, President Charles W. Penrose, and President Heber J. Grant. Elder Rulon S. Wells dedicated the site in the Salt Lake City Cemetery where EBW was buried next to Daniel H. Wells and close by the graves of their daughters Emeline Whitney Wells and Louisa Martha Wells Cannon.